The objectives of this project are to define the epidemiology, risk factors, transmission kinetics and pathogenesis of chlamydial infections in different population settings and different disease states using new molecular amplification techniques. Of increasing importance to this laboratory is the investigation of the role of Chlamydia pneumoniae in the development of atherosclerosis utilizing seroepidemiologic, pathologic, and animal models to address this issue. To address these objectives, we implemented non-invasive screening with molecular assays for C. trachomatis genital tract infections and documented extremely high rates of infection (27%) in sexually active female adolescents. The median time to repeat infection was six months, resulting in new recommendations to the PHS for routine screening of all sexually active adolescent females every six months for this common infection. In addition, we implemented a screening program of all female military recruits from 50 states and documented a prevalence of 9.2% among these women. By identification of chlamydia-infected individuals, we were able to document the efficiency of heterosexual transmission, which was 66% irrespective of the gender of the index individual. We conducted two mass antibiotic treatment trials aimed at lowering the prevalence and incidence of chlamydial genital and ocular infections respectively. Marked reductions in chlamydial infections were documented with subsequent control and prevention of blinding trachoma, which led to a combined WHO control program utilizing mass treatment with azithromycin. We have found evidence of C. pneumoniae infection in 50% of coronary and carotid atheromas by immunocytochemistry and/or PCR. We isolated C. pneumoniae from a heart transplant patient and we demonstrated in vitro that C. pneumoniae can infect and proliferate in coronary artery endothelial cells and aortic artery smooth muscle cells. In a preliminary animal model study, we were able to accelerate atheroscerotic lesions of the aorta with C. pneumoniae infection, and we were able to ameliorate the disease process following treatment with azithromycin. The significance of this project is that it addresses the most important questions regarding the most common sexually bacterial pathogen in the United States (i.e. C. trachomatis), estimated at four million new infections each year, emphasizing new non-invasive cost-effective diagnostic assays to help identify infected individuals and to implement better control programs. The research on C. pneumoniae infection has particular importance since it is a leading cause of community-acquired pneumonia and may be related to the development or acceleration of atherosclerotic heart disease, two of the leading causes of morbidity and mortality in our country and worldwide. - Chlamydia trachomatis, Chlamydia pneumoniae, sexually transmitted diseases (STDs), adolescents, infertility - Human Subjects & Human Subjects: Interview, Questionaires, or Surveys Only